News

Published: 8Mar2012

A research group led by Dr. A. Claudio Cuello of McGill University’s Faculty of Medicine, Dept. of Pharmacology and Therapeutics, has uncovered a critical process in understanding the degeneration of brain cells sensitive to Alzheimer’s disease (AD). The study, published in the February issue of the Journal of Neuroscience, suggests that this discovery could help develop alternative AD therapies.

New study points to possible new therapeutic approaches in
treatment of AD

A research group led by Dr. A. Claudio Cuello of McGill
University's Faculty of Medicine, Dept. of Pharmacology and
Therapeutics, has uncovered a critical process in understanding the
degeneration of brain cells sensitive to Alzheimer's disease (AD).
The study, published in the February issue of the Journal of
Neuroscience, suggests that this discovery could help develop
alternative AD therapies.

A breakdown in communication between the brain's neurons is
thought to contribute to the memory loss and cognitive failure seen
in people with AD. The likely suspect is NGF (Nerve Growth Factor),
a molecule responsible for generating signals that maintain healthy
cholinergic neurons - a subset of brain cells that are particularly
sensitive to AD - throughout a person's lifetime. Oddly, scientists
had never been able to find anything wrong with this molecule to
explain the degeneration of cholinergic neurons in patients with
AD.

This new study, however, has elucidated the process by which NGF
is released in the brain, matures to an active form and is
ultimately degraded. The researchers were also able to determine
how this process is altered in AD. The group demonstrated that
treatment of healthy adult rats with a drug that blocks the
maturation of active NGF leads to AD-like losses of cholinergic
functional units, which result in cognitive impairments. By
contrast, when treated with a drug to prevent degradation of active
NGF, the numbers of cholinergic contacts increased
significantly.

"Part of the difficulty in understanding this pathway has been
due to the technical challenges associated with differentiating the
active and inactive forms of NGF," explained Dr. Simon Allard, the
study's lead author and a postdoctoral fellow at McGill. "Our
proposed manipulations are different from existing therapies as
they aim to protect neurons from degeneration."

The authors suggest that these findings may lead to
pharmacological treatments that could delay the progression of
Alzheimer's disease. "This discovery should help design alternative
therapies," said Dr. Cuello, a Charles E. Frosst / Merck Chair.

This study was supported by the Canadian Institutes of Health
Research (CIHR) and an endowment from Alan Frosst and the Frosst
family.